Friday, June 29, 2012

The lost 300

"...what we’re talking about as a metabolic advantage is at the max about 300 kcal per day."

Ludwig's group using stable isotope doubly labeled water for Total Energy Expenditure assessment in 2012:

"During isocaloric feeding following weight loss, REE was 67 kcal/d higher with the very lowcarbohydrate diet compared with the low-fat diet. TEE differed by approximately 300 kcal/d between these 2 diets..."

I'm no great fan of metabolic advantage arguments. I like uncoupling proteins and the way that feeding electrons in to the respiratory chain at the FADH2/CoQ couple is significantly less efficient than feeding them in as NADH at complex I. Calories out can be in to heat (or in to adipocytes if you are so inclined). Your body can't harvest heat from the respiratory chain. We radiate that. There is a modest emphasis on NADH production from glucose and on FADH2 generation from beta oxidation... They feed in differently.

There have been some ugly arguments on the net over the years about metabolic advantage. Eventually the numbers give you some sort of idea as to who is correct and who is talking bollocks.

Quite why fat metabolism should be intrinsically more thermogenic than glucose metabolism is very interesting. Maybe there will be time to go in to this some day. But I live with a core body temperature at well above ambient, most of the time.

But for now, I simply find the number match between 2007 and 2012 rather gratifying.

58 comments:

I think the estimate of 300 kcal/day via Dr. Eades came originally from Richard Feinman's "Entropy" paper. It's nice to see a confirmation of his hypothesis, although I think the practical applications are modest.

Anyway, I have to admit that I am at least as gratified by who's wrong as who's right.

"The VLC diet group experienced some troubling hormonal changes that seem to be pretty common with this kind of diet. There were three main negative changes. The first and perhaps most troubling was an increase in cortisol, a stress hormone that may contribute to serious health problems over the long term (17). The second was a decrease in thyroid hormone, which is something that has been observed repeatedly with this kind of diet. Many of the negative effects that some people develop on long-term VLC diets (constipation, lethargy, poor sleep, hair loss, irritability) could be related to low thyroid function. This doesn't seem to be as much of an issue with moderate carbohydrate restriction."

"The second was a decrease in thyroid hormone, which is something that has been observed repeatedly with this kind of diet. Many of the negative effects that some people develop on long-term VLC diets (constipation, lethargy, poor sleep, hair loss, irritability) could be related to low thyroid function. This doesn't seem to be as much of an issue with moderate carbohydrate restriction."

One of the things that the media reports on this study have been emphasizing is the rise of CRP levels. However, if you look at the data, CRP levels did not really rise with the low carb diet. They were just reduced less than with the other diets, but were still lower than the pre-wieght loss baseline. These are the numbers provided by the study:

Pre-weight loss baseline CRP: 1.75 (0.44 to 4.61)Low fat diet CRP: 0.78 (0.38 to 1.92)Low glycemic CRP: 0. 76 (0.50 to 2.20)Low carb: 0.87 (o.57 to 2.69)So, it is not accurate to say that the low carb diet "raised" CRP as some of the articles published on the media say. The levels are still lower than pre-weight loss, just nos quite as low by a very very small difference (anything under 1 is considered normal CRP)

I have an under-active thyroid due to a Hashimodo disease which is pretty prevalent, as I understand, among people who have to take thyroid hormone in a pill form. Hashimodo is an autoimmune condition, many LCarbers report getting much better with other autoimmune issues (for example, on a LC diet I don't need an asthma medication). I have trouble believing that asthma, eczema, cat allergy , allergy on fish are all going better at the price of thyroid gland getting worse while immune system attacks it less.

The CRP is correlating with dietary fat, which is why it is lowest in the low fat group and highest in the high fat group. Who wants to bet the VLC diet group was swimming in omega 6 and was made relatively more inflammatory this way? Personally I eat flax daily and fish oil and salmon weekly at least. I suspect the keto group was spooning up mayonnaise.

Thyroid hormone and leptin follows gluttonous obese fat tissue, so it is not surprising the obesity resistance promoting diet (low carb) also has lowest leptin and lowest thyroid hormone. thyroid hormone does not promote thinness, thyroid hormone correlates with being a fatso, just like leptin.

Notice no one in the dummy corner is pointing out the low fat group had the highest leptin but they are all pointing out the low fat group had the highest thyroid hormone? Thyroid and leptin follow each other and they are products of fat tissue being acted upon by insulin. A lower thyroid hormone is good in the sense it is a marker of lack of fat growth.

Did you read Colpo's analysis? Fig. 3 makes it seem quite underwhelming. It'd be nice to see a study like this that limited confounders to single digits.

I had thyroid issues on LC that started causing nasty symptoms after ~5-months. I'm guessing my hormones were already out of whack from stress and my prior sugar-fuelled diet was probably acting as a crutch for something. Micronutrition could be another factor (low iodine, Se, Cu, Mg etc).

The real problem with this study is that it only lasted 4 weeks. Every longer lasting study shows the LC diet being much more efffective during the first 2 months, after which weight loss slows. By 6 months even in studies, like this one, where food is provided, weight loss slows to a crawl. And over the long term the diet corresponding to what was called the GI diet in this study (but which is really a Zone diet) has a better track record for dieters' ability to maintain.

I'm a huge fan of the LC diet for its ability to lower blood sugar, but it is harder for most people to maintain over the long term, and when they don't maintain they tend to end up with worse health because they've learned that eating fat is healthy, which it isn't once carbs go over 150 g a day. The research supporting this is discussed in my new book.

@Jenny all valid points, but IMO a lot of the issues with failing to maintain the diet is a direct result of a lack of social/medical support for the LC diet. Studies like this will hopefully change that one day.

When the LC diet is followed indefinitely, it is wildly successful for glucose intolerant and obese people. These people cannot improve as well by any other therapy. A lack of long term adherence is directly proportional to the horde if ignorant commenters.

I am thankful for my autie schizoid nature which allows me to look at people as if they were (really stupid) aliens. I feel no compulsion to join them in group think, to forfeit my own logic and self analysis. This is the main reason I have been long term successful with LC, a selective social lobotomy.

I don't know what hope other people have for long term following LC diets, making a pariah out of yourself and having not even the support of your doctors who all wish you would eat "normally" to be ideally healthy. Sad.

One of the problems with high-carb diets is that they require higher levels of T3, which places greater stress on the thyroid gland and increases the need for iodine.

Some have suggested that modern average levels of T3 are 1.5 times higher than they were before the advent of agricultural carbohydrates, and that iodine deficiencies might be caused by an abundance of dietary carbs rather than lack of iodine in the environment.

I wonder if people who experience plateau's on LC is down to underlying metabolic disorders eg some level of insulin and/or leptin resistance preventing them from becoming "true" fat burners?

My n=1 is that a "conventional wisdom healthy diet" plus exercise got me (a late forties 5'9" 205lb male) to 162lbs, further elimination of carbs got me down to 150lbs until I saw a photo of me one xmas and realised I looked emaciated (it was quite a shock) despite having a roll of fat around my middle - my athletic performance had tanked too but I had allsorts of rationalised explanations for that - just not that I had burned all my lean mass(!)

I upped the carbs and fat (a little) and cut back on exercise duration and drifted back up to approx 168lbs still with a roll of fat but clearly stronger and looking OK.

I tried to cut back on calories to about 1800/day keeping protein high, fat low and carbs moderate (main source oats at approx 200g/day and a few potatoes in the evening) and consuming skimmed milk - as a low fat source of protein - approx 6l/week whilst doing approx 1hr of relatively high intensity exercise/day.

Under this regimen my athletic performance was maintained as was my weight, then I learned how insulinogenic milk was (and I was consuming it regularly throughout the day) so I cut out milk and compensated for the lost protein with lean meat. I lost a few lbs and it was clearly fat lbs (mirror test) but then I plateaued so I started carb cycling and lost another few lbs but then plateaued. I looked a healthy weight but still had this roll of fat around my middle despite having "a healthy diet" with exercise.

The "milk" experience convinced me that a low insulinogenic diet was key and I started researching the high/fat low carb (paleo/primal) approach. Initially this started as 3 meals/day with the carbs at b/fast to zero carbs to 2 meals/day (skipping lunch) - my weight was stable as was my athletic performance. About this time I was reading about Intermittent fasting and also discovered Dr Kruse's Leptin reset protocol, I tried IF for 2 weeks (eating in a 4hr feeding window in the evening with almost zero carb) - I felt hungry during the day and was glad to eat by nightfall but oddly my weight went up by several pounds although I think this was lean weight as my muscles looked fuller and I didn't look/feel fatter. I read that Dr Kruse wasn't a fan of IF'ing if not leptin sensitive so I adopted the LRx protocol for several weeks (again 2 meals AM/PM) for about 1800kcal.

My weight remained stable and my hunger diminished so I decided to IF again, except this time I would eat one meal in the early evening

After a couple of weeks I was well adapted to the protocol - high fat, moderate protein, low carb, no hunger, no weight loss, excellent athletic performance - in fact I was noticing better athletic performance, lower fatigue and reduced CV stress for a given performance.

I assumed I was a fully adapted fat burner but still had a roll of fat around my middle. So what to do? My main calorie source was now fat so I figured cut the fat out. Which I do in a cyclical fashion - I cycle 2 days low fat with 1 day high fat - I don't feel hungry and the weight (Fat) is just melting off - from approx 15% BF I'm well on the way to single digit BF in a few weeks with no signs of plateauing.

This has taken the best part of 5 years of self experimenting, plateau's and pain galore but I now truly believe I've cracked it, you have to become a fat burner, increase insulin and leptin sensitivity through diet and exercise (if you can) and then restrict fat to become truly lean and finally have a high fat/moderate protein/low carb diet for maintenance.

bongo, The Good Doctor does not weigh 900lb and I bet he washes occasionally. It's his "science" which stinks. There is no gorilla.

Sam (and bongo), The TSH levels say it all. Nice link Sam. Might post on the T3 levels as they are meaningless without consideration of both TSH and degree of binding to thyroid binding globulin. You need free T3. Happens clinically occasionally. Free T3, love the name, it's an expensive test!

john, I'll look them up. I expected the adipose tissue IRKO mice to be thin and diabetic. Not that simple. You have to look at these KO mice very carefully...

Isabel, Woo and bill, the LC phase also seems to have the biggest gap between PUFA+MUFA+Sat and total fat intake...

Jenny, the social pressure on long term LC eaters is intense. I'm like Woo. I couldn't give a monkey's about what people think regarding my odd dietary habits. But my wife is very surreptitious with her lunch at work and another LCer tells her workmates the double cream she eats is low fat yogurt. Turning society around will take time, then we'll see how hard LC really is. And if it's a disaster!

Javeux, Colpo's analysis is the worst I've ever seen him do. He would have done better if he had any supportive data, which he doesn't. You really have to feel sorry for him. The TEE was up because the subjects cheated is the explanation, if I read him correctly. Hysterical when you think they cheated only in direct proportion to the carbohydrate content of the diet in this triple cross over study, using the same folks throughout with randomised order for degree of carbohydrate restriction!

"I'm a huge fan of the LC diet for its ability to lower blood sugar, but it is harder for most people to maintain over the long term, and when they don't maintain they tend to end up with worse health because they've learned that eating fat is healthy, which it isn't once carbs go over 150 g a day."

This doesn't make sense to me. Assuming you're right about fat being very bad past 150g of carbs, and that the problem is that they learn that fat is always good, here's a simple solution: when they start low carb, teach them that fat is healthy only on low carb. Problem solved!

Another oddity from my point of view is that we're assuming that if you can't stay on low carb you have to skip right over the "low GI"/"Zone" and go straight to eating tons of high GI carbs. Again, why can't we just tell them: if you can't stick with low carb, the next best thing is low GI.

Let me state from the beginning how much respect I have for you. Let me then seriously but respectfully disagree with your blanket statements.

"Every longer lasting study shows the LC diet being much more efffective during the first 2 months, after which weight loss slows. By 6 months even in studies, like this one, where food is provided, weight loss slows to a crawl. "

Do I not exist? I guess not, because my weight loss has been consistent now for a year. Have I had plateaus? Of course. And when they come, I reduce the nuts and berries, cut my protein at lunch by 1 oz, and it gets going again. You can also easily go over to the Atkins forum and meet many 150+ losers, who've been losing weight well for more than 18 months to 2 years. Are they lying? If not, what's different about them than other people?

That's the question to ask.

But all diets require tweaks because as you lose weight on any diet your metabolism slows a bit and also as you get smaller your basal energy needs decrease anyway. I'm really hurt that you just dismiss people like me out of hand, as if our experiences don't exist.

Yeah, some people do stall long-term - they are profoundly insulin resistant and frankly need metformin. But the low-carb diet isn't to blame for that. Not all damage can be healed.

"but it is harder for most people to maintain over the long term,"

Then how come I personally know so many who have been living this way since at least 1999? Are you seriously arguing that low-fat is easiest to maintain? Do you have to invalidate so much known experience to make your point? I really feel like you're trying to erase the successes myself and of so many I know with this statement.

I agree with the others that many people who fall off the diet do so because they 1 - don't have a well-formed plan (they start what Westman calls the "Chet Atkins" diet) 2 - need metformin, which they can't get or can't tolerate 3 - lack social and medical support.

All these problems are soluble, they are not inherent to low-carb. Frankly the guys with the best answers to the issues you pose are Westman and Volek; pity they don't talk to the community more often.

Ya, it personally puzzles me when it is claimed that LCarbing is hard. I am a veteran-dieter, on LC diets since 2007. It is the first time in my life I managed to stick to something for 5 years. Out of personal experience I can tell that there are two most difficult things to achieve on any diet - to tolerate hunger and to maintain moderation.( a "golden middle" is hard to achieve in anything in life) I am not even talking about loosing weight at the moment. What exactly makes LCarbing so particularly hard if it takes care of hunger and doesn't require from your to keep a precise balance between components of your menu or counting calories? May be I am also socially defective as well and it prevents me from the full appreciation of public oppinion. Well, good for me then. I am also got rid of long list of magical conditions. Am I the only one with such experience? Are there more people who would experience the return of swollen ankles, eczema, crappy moods together with the return of holy grains? For people like me the fraze " it is harder for most people to maintain over the long term," sounds like complete nonsence.

If thyriod regulates LDL receptors and these are also regulated by the amount of PUFA in the membranes, then the cross-talk between PUFA (mainly EPA, DHA, AA) and thyroid is maybe what we should be looking at (inuit diet = lots of PUFA, just saying).There are a couple papers on the thyroid-PUFA crosstalk on PubMed.

Also; maybe 300 kcal thermogenesis is optimal in a cold spot like the Arctic. Or Scotland.

@ Galina - you are not the only one. Over the last 18 months I have (through low carb intake) lost 55 lb but more importantly, gained remission from a lot of nasty symptoms of metabolic syndrome.

The weight loss has tapered off as my energy requirements have reduced (since I am not carrying the fat around). When I hit plateaus I tweaked things, like reducing calories overall, or going back to lower carbs (if the carbs had started to drift back up again). I don't believe my metabolism has slowed - I have much more energy than before and I am resistant to cold.

I have rarely experienced any hunger in that time - far less than when I was eating a "sensible" balanced diet of plentiful "low GI" carbs, adequate protein and moderate fat. On this "sensible" regime I was often overtaken by ravenous hunger for sugar and bread.

In short, I have found through trial and error that low carb=low hunger, as long as I have enough fat. I suspect my low carb diet is a much easier regime to stick to than low fat. I get to eat delicious things like Hollandaise sauce with my salmon and green salad. This compensates me for not being able to have the bread roll with dinner.

I don't have to go to work so it is easy to arrange meals the way I want to most of the time. Socialising is the big problem. People who have your best interests at heart want to press their idea of a healthy diet on you. They mean well and it's hard to say no. But I look at their big bellies (carb-eaters) and their crepe-y skin (low fat dieters). My belly is now pretty flat and my skin is flexible and moist and I think - I may be going against the grain but what I am doing is working; what you are doing is not working.

I agree LC is the easiest diet I have ever been on. Because when ever I am hungry, I can eat. There need never be hunger for most on LC. However, I have known a few VERY obese people for whom even VLC would not fully help. Sure they lost a bunch of weight, but still needed too lose at least 100 or 300 more and could not do it, even exercising and eating nothing but meat and not even eating much. Some of these people can be 10 times more motivated than I ever was to follow every LC rule to the letter! There are still some issues that need solving. VLC does not fix everything in everyone and I have heard too many stories of thyroid problems and exhaustion on long term VLC, especially in women. I know one person who cannot seem to make the passage into ketosis/gluconeogenesis. Instead she just gets very sick and sicker for several weeks until she eats carb. Is her liver too weak to do it? Could be there are special nutritional needs for the very obese to recover? Anyway, I don't think it is yet time for lowcarbers to pat themselves on the back and say the job is done and just poopoo on any naysayers. The best lessons are learned from those who disagree with you! ;-) -Eva

My guess is people who claim to have thyroid issues are simply not eating enough. So, when they claim their thyroid issues were "cured" with carbs, I have to wonder if the the carb intake simply increased their total energy input. So, had they simply eaten more (fat or protein), would they have seen similar improvements?

"I don't think it is yet time for lowcarbers to pat themselves on the back and say the job is done and just poopoo on any naysayers."

It is much more in LC diets application than just carb counting, but reduced hunger and increased energy work in your favor. I think it is impossible to do a job for somebody who is 400 lb by just applying a VLC diet. What are "LC rules"? In order to loose more than 20 lb many people have to tweak their diet, observe their reactions, to be creative as opposite to follow some universal LC rules . I pat my back because I managed to apply LC diet in a creative way and regained my health and lost weight despite being middle-aged woman with under-active thyroid gland. I just want to add that the type of thyroid hormone replacement may play a role. I now use a natural desiccated thyroid instead of Synthroid, and can tell that I don't experience cold sensitivity and don't need more sleep now. I think it is a good idea to check Wooo's blog, especially the post http://itsthewooo.blogspot.com/2012/03/insulin-hypothesis-is-not-same-as-cih.html . She lost 180 lb of 300, and it required much more than LCarbing .

I think you are probably right. The studies of reduced t3 or increased rt3 are mostly hypocaloric and sometimes vegetable oils; butter, coconut oil, and cream are less "efficient" than sucrose.

In ad libitum, the evidence isn't that clear. There is one rat study where the low carb, high sat fat [Crisco] rats had higher t3 than sucrose, starch, or glucose rats. As Woo says, high t3 can simply go along with the "standard" indicators or "metabolic syndrome." When t3 uptake is measured, there is usually no significant difference, but I don't know much about that test.

Though t3 may often partly indicate metabolic syndrome, it's hard to argue against the work of Barnes and others, where thyroid supplementation is quite helpful. William Kountz has a book about thyroid hormones and vascular degeneration, but I don't know if it's widely available. Maybe metabolic rate a better indicator of health than thyroid hormone status? Many think that a slow metabolism is beneficial, but I don't see why that is the case.

@Galina, it's true, for me also there was a lot more to losing (even just 55lb) than counting carbs and eating meat. It was difficult at first for me to overcome the "fat is bad" brainwashing and I ate too much protein at first, which I now realise turns to sugar. There are also some supplements I would not be without, particularly alpha lipoid acid, B6, chromium GTF and fish oil.

Not saying lc doesn't help a lot of people, me included. And not saying we should not pat ourselves on the back for our OWN accomplishments, just saying for any diet, including lc, it's a good idea to watch out for the assumption that anyone who cannot succeed on lc simply isn't doing it good enough, hard enough, carefully enough, etc. (and there are plenty of people who say/insinuate just that). I am just saying, lc may not be the answer to all and that we should keep looking.

And I am not saying that NO really heavy people can ever get totally trim using it, only that a lot don't, and I am not talking about just a few vanity pounds and the guy who is complaining that he/she does hot have the body of a supermodel yet.

The 'rules' are all the typical tweaks, avoid grain oils, exercise, be cautious of excess protein, cut out diary and cheese, IF, etc. Yes, there are plenty of 'rules' that you get told you are probably not doing if it's not working for you. Also, there is the problem of reactive hypoglycemia that seems to develop in some after losing weight on lc. Cutting protein does not always fix it either. WHat is the solution then other than to eat a bit more carb to block the hypo? If there is another solution to the hypo prob other than just cutting protein, i'd like to hear about it. Also, sometimes the issue of not eating enough food does seem to get ignored, a problem that seems to happen on vlc mostly. IMO, the right diet should hot accidentally cause you to starve yourself to illness. Anyway, my whole point was maybe we should look at the naysayers to lc carefully.

I plan to stay on moderate/lc myself and I think it's the general right approach but I also think the more educated naysayers are typically the ones that will show me areas that are still lacking and where I can learn the most. That is why when someone comes and brings up issues of increased cortisol levels or developing thyroid problems, I listen with interest and think hard about it. We are not even close to really understanding all the metabolic pathways or how to recover many of our sick people who have not found full relief on lc. Until that comes, I don't think it's time to sit back, stop considering criticism and think we already know all we need. I like lowcarb but I think we are still missing some pieces to the puzzle so we can improve it even more. Could be that micronutrients are part of what we need to understand better. Big pharma would rather study medications to give you than nutrients you might be lacking. That's why I am always interested when people come and point out potential areas of problem with lc. Those naysayers are a gift in that they expose all chinks in the system so that we may continue to improve.

Also, personally, I think a big contributer to difficulty staying on lc is that sugar and wheat are addictive and sugar is tasty and they are everywhere. Like any addiction, it's easier to fall back into it when temptation is so often waved in your face. But personally, I could give a rat's butt about what other's say about my diet. I enjoy eating ribeye to control my weight instead of cardboard flavored rice cakes. But I do often feel sad to see really heavy people struggling with the worst possible advice eating grain and crap and getting sicker and then being told they are just greedy pigs and it's all their fault. IMO, it's the cruelest injustice, so in the regard, the media really does peave me at times. LC may not solve everything but it sure does help a lot more than the alternatives.

Good point. That's why it's not a great idea to restrict yourself to under 50g/day of carbs over a length of time that results in you losing your hair or feeling like dirt. Having tried it, I find it's also very difficult to eat that small a quantity of carbs, and lucky for me I can thrive on 75g/day. If I found I could not maintain the desired body weight at 50g/day of carbs, I would use a cyclic ketogentic diet, and/or intermittent fasting. If you can't live well on carbs, you keep working until you find the low carb solution. It's not a 900 pound gorilla, it's a puzzle to solve for yourself to meet your individual needs.

Eva, some people with diabetes/bad insulin resistance won't be able to lose fat without medical treatments such as metformin. Other people have under-active thyroids but lose weight easily with thyroid supplementation. No doubt other disorders exist that make weight loss difficult (absent treatment).

Given the above, I don't know of any sensible person who would want to deny that there are people for whom low carb is not enough, or not enough on its own, to address their obesity.

Jama study VLC guys mean maintenance TEE was 3137kcal. So, 30% protein=235g and 10% carbs=78g.This is very high protein and 'not so low' carbs. They probably relied on gluconeogenesis. Add protein thermogenic effect to this and extra 300 calories doesnt sound strange any more.I'm not sure if dietary fat played much role here.

Why do you devise macronutrient ratios from TEE when there's diet composition table available in the study? VLC diet was 50g carbs, 150g protein (25g more than in run-in diet, I doubt this difference in protein can account for 300 Cal difference in TEE).

There is a bell-curve distribution of inherited need for macronutrient division.

VLC on one end (if you do not get epileptic seizures unless you eat a ketogenic diet, then you did not inherit a need for a ketogenic diet), HCLF on the other (people who are skinny and highly functional long-term on HCLF: "hard-gainers", Colpo, Guyenet). The avg person needs 40% cals from carb, 40% from fat, 20% from pro.

If people from the middle of the curve ate VLC, I can certainly see that not working for them, maybe even manifesting as symptoms of hypothyroid (as actual hypo myself - TSH 12 - I well know there are so many symptoms that CAN be hypothyroidism). Such people would experience huge relief of such symptoms by going to the aforementioned 40% carb etc.

Too many people extrapolating from their own personal experience -> everyone.

Also, although there's no reason for anyone who is lactose tolerant not to drink organic milk, a liter per day is a bit much. You mentioned its insulinogenic property (it is liquid carbs), but I also note it's excess calcium, especially relative to magnesium. 1 - 2 cups per day probably better than either none or a liter.

@jeffrey,couldn't you acquire an epileptic requirement for ketogenic diet by suffering neuronal damage in utero or in partum, or during development, without inheriting it?Couldn't you acquire a metabolic requirement for ketosis, at least temporarily, by damaging neurons through overindulgence in deep fried sweetened batter, soda, trans-fat cake, and the other toxic treats of the SAD?

Also you say "no reason for anyone who is lactose tolerant not to drink organic milk"but there are many immunogenic components to milk that one can be sensitive to - BCM7, IGA, even casozepine might be a bit much for some grown-ups.Not disagreeing with the rest of your statement, just think characterizing milk intolerance as lactose-based is unhelpful because next thing some idiot doctor stuck in the past will test you for lactase and tell you you're imagining things.

In HF mice, there was a shift in the circadian oscillations of plasma parameters together with an inhibition of PPP activity and a decrease in phosphorylated AMP-dependent protein kinase and fatty acid synthase. In a second experiment, HF mice were forced to adhere to a circadian pattern of food intake similar to that in control animals. In this case, BW, adipose tissue, morning plasma parameters and PPP activity appeared to be normal. These data indicate that disordered feeding behavior can trigger BW gain independently of food composition and daily energy intake.

http://www.ncbi.nlm.nih.gov/pubmed/21406612

Might have enough of this soon to set up shop as a third option to FRH and CIH.It's all about adipose 11β-hydroxysteroid dehydrogenase type 1now.

Hi all, just back from a wedding in Peebles, lovely extended weekend and utterly knackered. Scotland: Anyone buying 2 litres of bottled water on a Sunday morning is assumed to be overhung! I miss the place. Even though we got glutened in Maryhill.

George, I was working towards 11β-hydroxysteroid dehydrogenase type 1 via this paper

http://www.ncbi.nlm.nih.gov/pubmed/14763916

which mostly amused me by showing that anyone pontificating on the catastrophic skyrocketing (jk) of 24h urinary cortisol may make incorrect predictions about the good or bad effects of LC diets on the cortisol metabolism of obese people. Take home message; go LC asap if you want to fix your HPA axis, even before weight loss occurs. The paper is written in the worst style possible, but that does seem to be the executive summary.

Jeffery, I would view things fundamentally differently. There is a bell shaped curve of the ability to survive starvation. Most folks do OK and would be fine on LC. Some would do really well, ie yourself, with a shut down metabolism and a TSH of 12. At least in terms of surviving a month or so. You might not do well to maintain this state (or its mimic, ketogenic eating) longer than the next carbohydrate meal, assuming the TSH spike is directly carbohydrate related. Others do really badly, I think it is mnature who develops severe symptomatic hypoglycaemia on LC (and presumably on water fasting). I would certainly wonder which of these traits might actually be acquired or epigenetic rather than carried in the nuclear genes. But an interesting observation never the less. But to me starvation is an ubiquitous selection pressure. Macronutrient ratio seems utterly ephemeral cf the rigidities and predictability of starvation.

blogblog, I would agree if you included C57BL/6J in your descriptor of mice or rodents in general. Real mice, fed real fat, do fine. But no one studies them except by accident as control groups in studies where the genetically modified study mice are not B6 derived. So we get real wild types as controls.

Manythings, better watch what advice you give. If you have HYPOglycemia, you would absolutely not want to take metformin. Metformin is for HYPERglycemia (which she does not have). In fact, I know of no medication for hypoglycemia that one could hope to get from a doctor, other than carbs. Some people do find overall blood sugar swings to calm down and maybe even normalize on LC but considering that she actually developed hypoglycemia after going lc, there isn't much hope for lc fixing it.

Plus it's dangerous and extremely unhealthy to have tanking blood sugar levels after every meal. She has been experimenting now with small amounts of fruit at each meal to try to block the hypo. We are not sure what causes the hypos, but one guess is lc lowers insulin resistance but for some reason, the levels of insulin released do not lower in concert. Could be that a med for partially blocking insulin production might help, but that's hypothetical on my part unless someone has better info.-Eva

I believe the insulinotropic properties of milk are (primarily?) down to a couple of BCAA's not the lactose per se.

Besides the Ca issue you already mentioned there's also the IGF-1 stimulating property of milk too. I'm presently of the opinion that there's not much of a good reason to routinely consume liquid milk. Although I'm supplementing Iodine as a result (UK produced Milk being a useful dietary source).

Ahhh the old carbs before/protein after w/o paradigm, really?

I can only speak for myself but I'm doing pretty well on 1xHFMPLC meal/day - I don't feel the need to "fuel" anything, certainly not by carbs at any rate.

Now I'm aware of studies that show increased substrate utilisation immediately post workout but equally I understand (not seen any ref's though) that IF'ing also does the same - markedly for protein by accounts.

I currently suspect that as long as I keep calories sufficient that timing doesn't really matter, if it did I would expect either no improvements or even a deterioration over time.

However, this isn't religion for me, I'm open-minded, but minded at the moment to see how far I can get without resorting to carbs, frequent feeding, this before that, no this after 6pm ya-da, ya-da noise you hear all over the place.

@ blogblog,R D Feinman turned it neatly around by stating that the high-fat diet in mice is the equivalent of the low-fat diet in humans.Perhaps high-fat feeding in (some) rodents mimics DNL.

@Peter, nice paper.What are the three most important factors that determine the effect of any hormone?Location, location, location.We wouldn't worry so much about how much was in the serum sample, if we could learn just as easily where it was going in such a hurry, or where it just came from.

Yes, action at site of action is which matters. I did write a post looking at the relevance of T3 vs free-T3, vs receptor bound nuclear T3, vs cerebral nuclear T3 and why TSH (which goes DOWN on LC, certainly for the study folks) might be a window on to the later but Peebles got in the way and it all seems a bit old hat now. Might still tidy it up and hit post with a mention of the cortisol paper... Trouble is that work punishes you for 2 days off with a Bad Rota for the following week!

Peter, I love your blog. I am continually amazed at the nonsense blogged about about the VLC diet in blogosphere. They all need to take a course in neural lipid chemistry. I touch on that nonsense in this blog below. Peter thoughts become things for patients. Those things become reversals of fortune and illness. What I have seen written is done by people who just do not care for humans. They come from people in a lab who work on mice.

The number "300" also comes up in Wolfgang Lutz excellent book "Life Withoug Bread." http://www.amazon.ca/Life-Without-Bread-Low-Carbohydrate-Diet/dp/0658001701#_ He states that a healthy diet is one composed of no ore than 72 g or carbohydrate (or roughly the equivalent of 6 slices of bread). This works out to just under 300 calories of carbohydrate. This used to be the old recommendation to diabetics before the discovery of insulin.

Purely self-reporting, but in the NWCR studies, those maintaining weight loss on a low-carb diet ate an average of 497 more calories per day than those on a low-fat diet. They alsso reported less weekly exercise, and less "dietary restraint" (which I believe is jargon for not eating even though you're hungry).

Be careful not to be confused by the introductory phrase: "Only 10.8% of participants reported losing weight after a low-carbohydrate diet."

That sounds as if about 90% of the low-carb dieters failed to lose weight. In fact, what it means is "Only 10.8% of the people enrolled in the NWCR are low-carb dieters."

But that's about 500 calories, not the magic 300. Of course, it's also for weight maintenance rather than weight loss...

About Me

I am Petro Dobromylskyj, always known as Peter. I'm a vet, trained at the RVC, London University. I was fortunate enough to intercalate a BSc degree in physiology in to my veterinary degree. I was even more fortunate to study under Patrick Wall at UCH, who set me on course to become a veterinary anaesthetist, mostly working on acute pain control. That led to the Certificate then Diploma in Veterinary Anaesthesia and enough publications to allow me to enter the European College of Veterinary Anaesthesia and Analgesia as a de facto founding member. Anaesthesia teaches you a lot. Basic science is combined with the occasional need to act rapidly. Wrong decisions can reward you with catastrophe in seconds. Thinking is mandatory.
I stumbled on to nutrition completely by accident. Once you have been taught to think, it's hard to stop. I think about lots of things. These are some of them.

Organisation (or lack of it)!

The "labels" function on this blog has been used to function as an index and I've tended to group similar subjects together by using labels starting with identical text. If they're numbered within a similar label, start with (1). The archive is predominantly to show the posts I've put up in the last month, if people want to keep track of recent goings on. I might change it to the previous week if I ever get to time to put up enough posts in a week to justify it. That seems to be the best I can do within the limits of this blogging software!